The Interferons: Characterization and Application
by Anthony Meager (Editor)
Product Details
* Hardcover: 460 pages
* Publisher: Wiley-VCH; 1 edition (May 1, 2006)
* Language: English
* ISBN-10: 3527311807
Book Description
At long last, the first book to cover all important areas of interferon science in one volume. Top scientists, including many pioneers in the field, highlight the role of interferons as research tools and as therapeutic agents in clinical applications. Edited by an experienced interferonologist, chapters include discussions of interferon genes, Type I, II and III IFNs, as well as their induction, production and purification, receptors actions, measuring IFN activities and anti-IFN antibodies, as well as the evolution of viral defense mechanisms.
For immunologists, cancer researchers, medicinal chemists, cell biologists, developmental biologists and the pharmaceutical industry.
Contents
Preface XIII
List of Contributors XV
Color Plates XIX
Section A Molecular Aspects, Introduction and Purification 1
1 Type I Interferons: Genetics and Structure 3
Shamith A. Samarajiwa, William Wilson and Paul J. Hertzog
1.1 Introduction 3
1.2 The Type I IFN Genetic Locus 4
1.3 Type I IFN Genes 7
1.3.1 IFN-a 7
1.3.2 IFN-b 7
1.3.3 IFN-o 8
1.3.4 IFN-k 8
1.3.5 IFN-e 9
1.3.6 IFN-z (Limitin) 9
1.3.7 IFN-t 9
1.3.8 IFN-d 10
1.3.9 IFN-n 10
1.4 Type I IFN Gene-regulatory Regions 11
1.5 Evolution of the Type I IFNs 15
1.5.1 Vertebrate IFN Genes 15
1.5.2 The Expansion and Divergence of the IFN Genes 20
1.6 Natural and Induced Mutations in IFN Genes 21
1.7 Secondary Structural Features of Type I IFNs 22
1.7.1 Conserved Amino Acid Residues 22
1.7.2 Post-translational Modifications of Type I IFNs 23
1.7.3 Conserved Cysteine Residues and Disulfide Bond Formation 24
1.8 The Structure of Type I IFNs 24
References 27
2 Activation of Interferon Gene Expression Through Toll-like Receptor-dependent
and -independent Pathways 35
Peyman Nakhaei, Suzanne Paz and John Hiscott
2.1 Introduction 35
2.2 IFN-b Gene Transcription 39
2.3 IRF Family Members 40
2.4 Role of IRFs in Virus-mediated IFN Activation 41
2.4.1 IRF-3 41
2.4.2 IRF-5 47
2.4.3 IRF-7 48
2.5 IFN Signaling Pathways 49
2.5.1 TLR-dependent Signaling to IFN Activation 49
2.5.1.1 TLR Overview 49
2.5.1.2 TLR-3 Signaling 51
2.5.1.3 TLR-4 Signaling 53
2.5.1.4 TLR-7 Signaling 57
2.5.1.5 TLR-9 Signaling 57
2.5.2 TLR-independent Signaling 58
2.5.2.1 Retinoic-inducible Gene (RIG)-I Signaling 58
2.5.2.2 Melanoma Differentiation-associated Gene-5 (mda-5) 59
2.6 Conclusions 61
References 61
3 Interferon Proteins: Structure, Production and Purification 73
Dimitris Platis and Graham R. Foster
3.1 Introduction 73
3.2 The Structure of Type I IFNs 73
3.3 Production and Purification of Type I IFNs 75
3.3.1 Leukocyte-derived IFN – First Steps in Producing Commercial IFN 75
3.3.2 Lymphoblastoid IFN – Towards more Reliable Supplies of IFN 76
3.3.3 Cloned Type I IFNs – An Inexhaustible Supply of Therapeutic
Material 76
3.4 Long-acting IFNs 78
3.5 Summary 79
References 80
4 Interferon-g: Gene and Protein Structure, Transcription Regulation, and
Actions 85
Ana M. Gamero, Deborah L. Hodge, David M. Reynolds, Maria Cecilia Rodriguez-
Galan, Mansour Mohamadzadeh and Howard A. Young
4.1 Introduction 85
4.2 IFN-g Gene Structure and Regulation 86
4.2.1 Transcriptional Regulation 86
4.2.2 Epigenetic Regulation 88
4.2.3 Post-transcriptional Regulation 90
4.3 IFN-g Signal Transduction 90
4.3.1 The JAK–STAT Signaling Pathway 91
4.3.2 Activation of Alternate Signaling Pathways 92
4.3.3 Regulation of IFN-g Signaling 93
4.4 IFN-g in Th Cell Development 95
4.4.1 Signaling Pathways Involved in T Cell Development 95
4.5 IFN-g and DCs 97
4.5.1 IFN-g and T Cell–DC Crosstalk 97
4.5.2 Signals through Toll-like Receptors (TLRs) Activate DCs and Influence
IFN-g Expression 99
4.6 IFN-g – Role in Tumor Development and Growth 100
4.6.1 IFN-g in Tumor Growth and Survival 100
4.6.2 Inhibition of Angiogenesis by IFN-g 101
4.6.3 Role of IFN-g in Promoting Immune Responses against Tumors 102
4.7 Summary 103
References 104
5 Interferon and Related Receptors 113
Sidney Pestka and Christopher D. Krause
5.1 Introduction 113
5.2 IFNs and IFN-like Molecules in Brief 113
5.3 The Receptors 114
5.3.1 Receptor Nomenclature 115
5.4 The Type I IFN Receptor 116
5.4.1 Discovery of the Type I Receptor Complex 117
5.4.2 Diversity of the Interaction of Type I IFNs with the Receptor 119
5.5 The Type II IFN (IFN-g) Receptor 121
5.5.1 Chromosomal Localization of the IFN-g Receptor Ligand-binding Chain
and Discovery of Two Chains Required for Activity 121
5.5.2 The IFN-gR1 Chain 123
5.5.3 The Second Receptor Chain (IFN-gR2) 123
5.5.4 The Functional IFN-gR Complex 124
5.5.4.1 Specificity of Ligand Binding 124
5.5.4.2 Specificity of the Interactions of the Two Chains 124
5.5.5 Specificity of Signal Transduction 124
5.5.6 Receptor Structure 125
5.5.7 Preassembly of the Receptor Complex 126
5.6 The IL-28R1 and -10R2 Receptor Complex 127
5.7 Overview of Multichain Receptors 128
5.8 Global Summary 128
References 129
6 Type III Interferons: The Interferon-l Family 141
Sergei V. Kotenko and Raymond P. Donnelly
6.1 Introduction 141
6.2 The Class II Cytokine Receptor Family (CRF2) and their Ligands 142
6.3 Genomic Structure 145
6.4 Receptor Complex and Signaling 148
6.5 Biological Activities 152
6.6 The Murine IFN-l Antiviral System 154
6.7 Evolution of the IFN Family 156
6.8 Therapeutic Potential 157
6.9 Conclusions 158
References 158
Section B Biological Properties 165
7 Biological Actions of Type I Interferons 167
Melissa M. Brierley, Jyothi Kumaran and Eleanor N. Fish
7.1 Introduction 167
7.2 Sources of Type I IFN Production and Secretion 167
7.3 Type I IFN Interactions with the Receptor Complex 168
7.3.1 Structure and Functional Regions of Type I IFNs 168
7.3.2 IFN Domains Mediating Interactions with IFNAR-2 168
7.3.3 IFNAR-2 Domains Mediating Interactions with IFNs 170
7.3.4 IFN-a Interaction with IFNAR-2 172
7.3.5 IFN-b Interaction with IFNAR-2 173
7.3.6 Type I IFN Interactions with IFNAR-1 174
7.3.7 IFNAR-1 Receptor Interaction with Glycosphingolipids 174
7.3.8 Residues in Type I IFNs that Mediate Biological Responses 175
7.4 Type I IFN-induced Signaling Cascades 175
7.4.1 The JAK–STAT (Signal Transducers and Activators of Transcription)
Pathway 175
7.4.1.1 The Importance of STAT-1 and -2 in Type I IFN Signaling 178
7.4.2 Other IFN-inducible Signaling Cascades 179
7.4.2.1 The CrkL Pathway 179
7.4.2.2 The IRS Pathway 179
7.4.2.3 The p38 Mitogen-activated Protein Kinases (MAPK) Pathway 181
7.4.2.4 The Vav Protooncogene and IFN Signaling 182
7.4.2.5 The Protein Kinase C (PKC) Family and IFN Signaling 182
7.5 IFN-inducible Biological Responses 183
7.5.1 IFN-inducible Antiviral Responses 183
7.5.1.1 PKR 186
7.5.1.2 20–50-OAS/RNase L 186
7.5.1.3 Mx 187
7.5.1.4 Other IFN-inducible Antiviral Effectors 188
7.5.2 IFN-inducible Growth-inhibitory Responses 188
7.5.3 IFN-inducible Immunomodulation 190
7.6 Summary 192
References 193
8 Interferons and Apoptosis – Recent Developments 207
Michael J. Clemens and Ian W. Jeffrey
8.1 Introduction 207
8.2 The Role of IFN-regulated Genes in the Control of Apoptosis 209
8.2.1 Proapoptotic Genes Induced by IFNs 209
8.2.2 p53 and IFN-induced Apoptosis 209
8.2.3 The Ribonuclease (RNase) L System 210
8.3 The Protein Kinase PKR and the Phosphorylation of Polypeptide Chain
Initiation Factor eIF2a 212
8.3.1 Regulation of Apoptosis by PKR 212
8.3.2 The Role of eIF2a Phosphorylation 212
8.4 IFNs and the Apoptotic Effects of TRAIL 215
8.4.1 TRAIL Induction 215
8.4.2 TRAIL Activity 215
8.5 Signal Transduction Pathways for IFN-mediated Effects on
Apoptosis 218
8.6 The Antiapoptotic Effects of IFNs 219
8.7 Conclusions 220
Acknowledgments 220
References 221
9 Viral Defense Mechanisms against Interferon 227
Santanu Bose and Amiya K. Banerjee
9.1 Introduction 227
9.2 Innate Immune Antiviral Defense Mechanisms of Host Cells 227
9.3 Evasion of IFN-mediated Antiviral Response 231
9.3.1 Nonsegmented Negative-strand RNA Viruses 232
9.3.1.1 Paramyxoviruses 232
9.3.1.2 Filovirus 242
9.3.1.3 Rhabdovirus 242
9.3.2 Segmented Negative-strand RNA Viruses 242
9.3.2.1 Orthomyxovirus 243
9.3.2.2 Bunyaviruses 243
9.3.3 Positive-sense ssRNA Viruses 244
9.3.3.1 Picornaviruses 244
9.3.3.2 Flaviviruses 244
9.3.3.3 Coronavirus 246
9.3.4 dsRNA Viruses 247
9.3.5 RNA and DNA Reverse-transcribing Viruses 247
9.3.5.1 Retrovirus 247
9.3.5.2 Hepadnavirus 248
9.3.6 dsDNA Viruses 248
9.3.6.1 Adenovirus 248
9.3.6.2 Poxvirus 248
9.3.6.3 Herpesvirus 250
9.3.6.4 Papillomavirus 252
9.4 Concluding Remarks 253
References 254
Section C Clinical Applications 275
10 Overview of Clinical Applications of Type I Interferons 277
Frank Mu¨ller
10.1 Introduction 277
10.2 Biological Effects 277
10.3 Type I IFN Products Currently Available or Under Development 278
10.4 Pharmacokinetics 284
10.4.1 IFN-a 284
10.4.2 IFN-b 285
10.5 Clinical Applications of Type I Interferons 285
10.5.1 Chronic hepatitis B (CHB) 286
10.5.2 Chronic hepatitis C (CHC) 288
10.5.3 Chronic hepatitis D (CHD) 290
10.5.4 Hairy Cell Leukemia (HCL) 290
10.5.5 Renal Cell Carcinoma (RCC) 291
10.5.6 Basal Cell Carcinoma (BCC) 292
10.5.7 Malignant Melanoma 292
10.5.8 Kaposi Sarcoma (KS) 292
10.5.9 Multiple Myeloma 293
10.5.10 Chronic myelogenous leukemia (CML) 294
10.5.11 Non-Hodgkinis lymphoma (NHL) 295
10.5.12 Laryngeal Papillomatosis 295
10.5.13 Mycosis Fungoides (MF) 296
10.5.14 Condyloma Acuminata 296
10.5.15 Multiple Sclerosis (MS) 297
10.6 IFN Toxicity 298
10.7 Type I IFNs in the Future 299
References 300
11 Clinical Applications of Interferon-g 309
Christine W. Czarniecki and Gerald Sonnenfeld
11.1 Introduction 309
11.2 IFN-g – The Molecule 311
11.3 FDA-approved Indications: Established Benefit and Risks 311
11.3.1 Chronic Granulomatous Disease (CGD) 311
11.3.2 Osteopetrosis 313
11.3.3 Adverse Reactions 314
11.4 Infectious Diseases 314
11.4.1 Mycobacterial Infection 314
11.4.1.1 Leprosy 314
11.4.1.2 Mycobacterium avium Infection 315
11.4.1.3 Tuberculosis (TB) 315
11.4.2 Leishmaniasis 317
11.4.3 Opportunistic Infections in HIV Disease 317
11.5 Infection Following Serious Trauma 318
11.6 Atopic Dermatitis (AD) 321
11.7 Idiopathic Pulmonary Fibrosis (IPF) 322
11.8 Systemic Sclerosis (SSc) 326
11.9 Radiation-induced Fibrosis 326
11.10 Chronic Hepatitis 327
11.11 Oncology Indications: Ovarian Cancer 329
11.12 Conclusions 330
References 331
Section D Measurement of Interferons and Anti-Interferons 337
12 Measurement of Interferon Activities 339
Tony Meager
12.1 Introduction 339
12.2 The IFNs: Mechanisms of Action, Protein Induction and Biological
Activities 340
12.2.1 Mechanisms of Action 340
12.2.2 Protein Induction 342
12.2.3 Biological Activities 344
12.2.3.1 Antiviral Activity 344
12.2.3.2 Antiproliferative Activity 344
12.2.3.3 Immunomodulatory Activity 345
12.3 Measurement of Biological Activities of IFNs 345
12.3.1 General Considerations 345
12.3.2 Biological Standards for IFNs 346
12.3.3 Practical Considerations for IFN Preparations 348
12.3.4 Antiviral Assays 349
12.3.5 Antiproliferative Assays 351
12.3.6 IFN-inducible Protein Assays 354
12.3.6.1 Bioimmunoassays 354
12.3.6.2 Enzyme Expression and Reporter Gene Assays 356
12.3.7 Assays Based on Intracellular Signaling Intermediates 361
12.3.8 Assay Design and Data Analysis 363
12.4 Regulatory Landscape 365
Acknowledgments 366
References 366
13 The Development and Measurement of Antibodies to Interferon 375
Sidney E. Grossberg and Yoshimi Kawade
13.1 Introductory Perspective 375
13.1.1 Immunological Perspective 375
13.1.2 Antibodies to Self-antigens 376
13.2 NAbs 377
13.2.1 Neutralization Bioassay Design 378
13.2.1.1 The Constant IFN Method 379
13.2.1.2 The Constant Antibody Method 380
13.2.2 Theoretical Analyses 382
13.2.3 Experimental Analyses 383
13.2.4 Standardization and the Reporting of Neutralization Results 383
13.2.5 A Solution to the Problem of NAb Unitage 385
13.3 Immunoassays for Non-NAbs 387
13.4 Epitope Analysis 388
13.5 Development of Antibodies during IFN Therapy 390
13.5.1 Antibodies to IFN-a 391
13.5.2 Antibodies to IFN-b 392
13.6 Summary 394
References 395
